Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections.[1] Other uses include for middle ear infections and travelers' diarrhea. With sulfamethoxazole or dapsone it may be used for Pneumocystis pneumonia in people with HIV/AIDS.[1][2] It is taken by mouth.[1]

Common side effects include nausea, changes in taste, and rash. Rarely it may result in blood problems such as not enough platelets or white blood cells. May cause sun sensitivity.[1] There is evidence of potential harm during pregnancy in some animals but not humans.[3] It works by blocking folate metabolism via dihydrofolate reductase in some bacteria which results in their death.[1]

Trimethoprim was first used in 1962.[4] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[5] It is available as a generic medication and is not very expensive.[6] In the United States 10 days of treatment is about 21 USD.[1]

Contents

1Medical uses

1.1Spectrum of susceptibility

2Side effects

2.1Common

2.2Rare

2.3Contraindications

2.4Liver and kidney problems

2.5Pregnancy

3Mechanism of action

4History

5See also

6References

7External links

Medical uses

It is primarily used in the treatment of urinary tract infections, although it may be used against any susceptible aerobic bacterial species.[7] It may also be used to treat and prevent Pneumocystis jiroveci pneumonia.[7] It is generally not recommended for the treatment of anaerobic infections such as Clostridium difficile colitis (the leading cause of antibiotic-induced diarrhea).[7]

Resistance to trimethoprim is increasing, but it is still a first line antibiotic in many countries.[8]

Spectrum of susceptibility

Cultures and susceptibility tests should be done to make sure bacteria is treated by trimethoprim.[9][10]

Escherichia coli

Proteus mirabilis

Klebsiella pneumoniae

Enterobacter species

Coagulase-negative Staphylococcus species, including S. saprophyticus

Streptococcus pneumoniae

Haemophilus influenzae

Side effects

Common

Nausea

Change in taste

Vomiting

Diarrhea

Rash

Sun sensitivity

Itchiness[11][12]

Rare

Can cause thrombocytopenia (low levels of platelets) by lowering folic acid levels; this may also cause megaloblastic anemia.[13]

Trimethoprim antagonizes the epithelial sodium channel in the distal tubule, thus acting like amiloride. This can cause increased potassium levels in the body (hyperkalemia).[14]

Can compete with creatinine for secretion into the renal tubule. This can cause an artificial rise in the serum creatinine.[15]

Use in EHEC infections may lead to an increase in expression of Shiga toxin.[16]

Contraindications

Known hypersensitivity to trimethoprim

History of megaloblastic anemia due to folate deficiency[17]

Liver and kidney problems

10-20% of trimethoprim is metabolized by the liver and the rest is excreted in the urine. Therefore, trimethoprim should be used with caution in individuals with kidney and liver impairments. Dosage adjustment is not needed for liver impairment but should be adjusted for kidney impairment.[18]

Pregnancy

Based on studies that show that trimethoprim crosses the placenta and can affect folate metabolism, there has been growing evidence of the risk of structural birth defects associated with trimethoprim, especially during the first trimester of pregnancy.[19] It may be involved in a reaction similar to disulfiram when alcohol is consumed after it is used, in particular when used in combination with sulfamethoxazole.[20][21] The trophoblasts in the early fetus are sensitive to changes in the folate cycle. A recent study has found a doubling in the risk of miscarriage in women exposed to trimethoprim in the early pregnancy.[22]

Mechanism of action

Trimethoprim binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF).[24] THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis.[24] Trimethoprim's affinity for bacterial dihydrofolate reductase is several thousand times greater than its affinity for human dihydrofolate reductase.[24] Sulfamethoxazole inhibits dihydropteroate synthase, an enzyme involved further upstream in the same pathway.[24] Trimethoprim and sulfamethoxazole are commonly used in combination due to possible synergistic effects, and reduced development of resistance.[24] This benefit has been questioned.[25]

History

Trimethoprim was first used in 1962.[4] In 1972, it was used as a prophylactic treatment for urinary tract infections in Finland.[4]

The Science of the total environment.Sci Total Environ.2015 Oct 15;530-531:140-53. doi: 10.1016/j.scitotenv.2015.05.080. Epub 2015 May 28.

Contaminants of emerging concern (CECs), including pharmaceuticals, personal care products and estrogens, are detected in wastewater treatment plant (WWTP) discharges. However, analytical monitoring of wastewater and surface water does not indicate whether CECs are affecting the organisms downstream

The Science of the total environment.Sci Total Environ.2015 Oct 15;530-531:11-7. doi: 10.1016/j.scitotenv.2015.05.091. Epub 2015 May 27.

One hundred-fourteen samples of wastewater (n=64) and surface-water (n=50) were inoculated in Slanetz-Bartley agar plates supplemented or not with gentamicin (SB-Gen and SB plates, respectively) for enterococci recovery. Enterococci were obtained from 75% of tested samples in SB media (72% in wastew

Salmonella enterica infections are common causes of bloodstream infection in low-resource areas, where they may be difficult to distinguish from other febrile illnesses and may be associated with a high case fatality ratio. Microbiologic culture of blood or bone marrow remains the mainstay of labora